Non-coding RNAs as emerging biomarkers in oral cancer

Oral squamous cell carcinoma (OSCC) represents the most prevalent malignancy of the oral cavity, accounting for over 90% of oral cancer cases and ranking as the sixteenth most commonly diagnosed cancer worldwide. Arising from the epithelial lining of structures such as the tongue, gingiva, buccal mucosa, lips, and palate, OSCC frequently progresses silently in its early stages, delaying detection and contributing to poor clinical outcomes. Advanced disease often manifests with ulceration, nodularity, and tissue invasion, highlighting the critical importance of early diagnosis. Traditional diagnostic approaches, including biopsies and visual inspection, while informative, are invasive, time-consuming, and limited in their capacity for early-stage detection. Recent advances in molecular biology have identified non-coding RNAs (ncRNAs) including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) as pivotal regulators of oral carcinogenesis. These molecules modulate gene expression, influence tumor progression, and exhibit remarkable stability in biofluids such as saliva and blood, making them promising candidates for noninvasive biomarkers. Emerging evidence demonstrates that distinct ncRNA expression profiles can serve as diagnostic and prognostic indicators, predict therapeutic response, and enable real-time monitoring through liquid biopsy approaches. This review summarizes the classification, biological functions, and mechanistic roles of ncRNAs in oral cancer, with a focus on their translational potential in precision oncology. We discuss current methodologies for ncRNA detection, highlight challenges in clinical implementation, and outline future perspectives for integrating ncRNA-based biomarkers into routine diagnostic and therapeutic frameworks. Harnessing these molecular insights holds significant promise for improving early detection, prognostication, and personalized management of OSCC, ultimately enhancing patient outcomes.